Inside and outside of virus-like particles HBc and HBc/4M2e: A comprehensive study of the structure

被引:2
|
作者
Egorov, V. V. [1 ,2 ,3 ,4 ]
Shvetsov, A. V. [1 ,3 ,5 ]
Pichkur, E. B. [3 ]
Shaldzhyan, A. A. [2 ]
Zabrodskaya, Ya. A. [2 ,5 ]
Vinogradova, D. S. [1 ]
Nekrasov, P. A. [2 ]
Gorshkov, A. N. [2 ]
Garmay, Yu. P. [1 ]
Kovaleva, A. A. [2 ]
Stepanova, L. A. [2 ]
Tsybalova, L. M. [2 ]
Shtam, T. A. [1 ,3 ]
Myasnikov, A. G. [1 ,3 ]
Konevega, A. L. [1 ,3 ,5 ]
机构
[1] Kurchatov Inst, Petersburg Nucl Phys Inst B P Konstantinov, Konstantinov Natl Res Ctr, Orlova Roscha 1, Gatchina 188300, Russia
[2] Russian Minist Hlth, Smorodintsev Res Inst Influenza, Prof Popov St 15-17, St Petersburg 197376, Russia
[3] Kurchatov Inst, Natl Res Ctr, Akademika Kurchatova pl 1, Moscow 123182, Russia
[4] Inst Expt Med, Academika Pavlova 12, St Petersburg 197376, Russia
[5] Peter Great St Petersburg Polytech Univ, Politehnicheskaya 29, St Petersburg, Russia
基金
俄罗斯科学基金会;
关键词
Virus -like particles; Hepatitis B virus core antigen; Influenza virus; Structural analysis; Cryo-electron microscopy; Molecular modeling; THIOFLAVINE-T INTERACTION; ANTIGENS;
D O I
10.1016/j.bpc.2022.106943
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatitis B virus core antigen (HBc) with the insertion of four external domains of the influenza A M2 protein (HBc/4M2e) form virus-like particles whose structure was studied using a combination of molecular modeling and cryo-electron microscopy (cryo-EM). It was also shown that self-assembling of the particles occurs inside bacterial cells, but despite the big inner volume of the core shell particle, purified HBc/4M2e contain an insignificant amount of bacterial proteins. It was shown that a fragment of the M2e corresponding to 4M2e insertion is prone to formation of amyloid-like fibrils. However, as the part of the immunodominant loop, M2e insertion does not show a tendency to intermolecular interaction. A full-atomic HBc-4M2e model with the resolution of about 3 angstrom (3.13 angstrom for particles of T = 4 symmetry, 3.7 angstrom for particles of T = 3 symmetry) was obtained by molecular modeling methods based on cryo-EM data.
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页数:7
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